ABSTRACT (CORE D: MESA Sample and Data Analysis) Cardiovascular disease (CVD) remains a leading cause of death worldwide, despite the success of statins in reducing LDL, a major risk factor for CVD. Immunity is believed to play an important role in atherosclerosis, in which plaque accumulates in the arteries and through its downstream effects, leads to CVD. The importance of various immune cell subsets on atherogenesis in mice have been demonstrated, yet these data are limited on alterations in immune cells during atherogenesis in humans. The goal of the proposed Program Project Grant (PPG) is to identify the regulation of immune cell function by lipoproteins and the crosstalk of these immune cells in human atherogenesis, building on a basis of cellular, biochemical and model system studies. The ultimate goal of these studies is to identify novel therapies targeting immune cell function to limit CVD initiation and progression. The PPG contains four projects that will study functional changes in immune cells and the immune cell cross-talk that occurs during atherosclerosis progression in humans using a well-characterized NHLBI-sponsored longitudinal clinical cohort, the Multi-Ethnic Study of Atherosclerosis (MESA), and the UVA Cardiovascular Cohort. Within the MESA cohort, all projects will utilize data and PBMC samples obtained at baseline (2000-2002), selected on the coronary artery calcium (CAC) score ? either low (CAC = 0) or high (CAC > 300). The purpose of Core D (MESA Sample and Data Analysis Core) is to establish the resource of MESA PBMC samples, coordinate the retrieval and use of data from the MESA baseline and follow-up examinations, and participate in the analyses of the immune markers (this PPG) with existing biomarkers and risk factors from MESA. Core D will be used by all projects of the PPG. In order to support the four projects, the specific aims of Core D are to (1) identify the MESA participants meeting critieria (CAC = 0 AU; CAC > 300 AU) with available PBMC samples and with at least two follow-up visits (to permit estimates of progression; (2) receive viable, frozen PBMC samples from the MESA Biochemistry Laboratory at the University of Vermont (Russ Tracy, PhD, Director) and establish an inventory for use by the individual PPG projects; (3) obtain MESA data relevant to the individual projects (biomarkers, risk factors, clinical events, other key variables and outcomes, other markers of immune function) and integrate the existing MESA data with the PPG project data for analysis; and (4) provide support for each PPG project in statistical analyses. Core D leverages the NHLBI investment MESA as a population laboratory with detailed imaging and biological samples and data to merge with the innovative studies of proposed in the PPG in order to advance translational research in limiting the initiation and progression of atherosclerosis that leads to cardiovascular disease.